Picein alleviates oxidative stress and promotes bone regeneration in osteoporotic bone defect by inhibiting ferroptosis via Nrf2/HO-1/GPX4 pathway.

Osteoporosis (OP) can result in slower bone regeneration than the normal condition due to abnormal oxidative stress and high levels of reactive oxygen species (ROS), a condition detrimental for bone formation, making the OP-related bone healing a significant clinical challenge. As the osteogenic differentiation ability of bone marrow mesenchymal stem cells (BMSCs) is closely related to bone regeneration; currently, this study assessed the effects of Picein on BMSCs in vitro and bone regeneration in osteoporotic bone defect in vivo. Cell viability was determined by CCK-8 assay. The production of (ROS), malonaldehyde, superoxide dismutase activities, and glutathione was evaluated by using commercially available kits, and a flow cytometry analysis was adopted to detect macrophage polarization. Osteogenic capacity of BMSCs was evaluated by alkaline phosphatase (ALP) activity, ALP staining, and Alizarin red S staining. The expression of osteogenic-related proteins (OPN, Runx-2, OCN) and osteogenic-related genes (ALP, BMP-4, COL-1, and Osterix) were evaluated by Western blotting and real-time PCR (RT-PCR). In addition, proliferation, migration ability, and angiogenic capacity of human umbilical vein endothelial cells (HUVECs) were evaluated by EdU staining, scratch test, transwell assay, and tube formation assay, respectively. Angiogenic-related genes (VEGF, vWF, CD31) were also evaluated by RT-PCR. Results showed that Picein alleviated erastin-induced oxidative stress, enhanced osteogenic differentiation capacity of BMSCs, angiogenesis of HUVECs, and protects cells against ferroptosis through Nrf2/HO-1/GPX4 axis. Moreover, Picein regulate immune microenvironment by promoting the polarization of M2 macrophages in vitro. In addition, Picein also reduce the inflammation levels and promotes bone regeneration in osteoporotic bone defect in OP rat models in vivo. Altogether, these results suggested that Picein can promote bone regeneration and alleviate oxidative stress via Nrf2/HO-1/GPX4 pathway, offering Picein as a novel antioxidant agent for treating osteoporotic bone defect.

Injectable, anti-collapse, adhesive, plastic and bioactive bone graft substitute promotes bone regeneration by moderating oxidative stress in osteoporotic bone defect.

The treatment of osteoporotic bone defect remains a big clinical challenge because osteoporosis (OP) is associated with oxidative stress and high levels of reactive oxygen species (ROS), a condition detrimental for bone formation. Anti-oxidative nanomaterials such as selenium nanoparticles (SeNPs) have positive effect on osteogenesis owing to their pleiotropic pharmacological activity which can exert anti-oxidative stress functions to prevent bone loss and facilitate bone regeneration in OP. In the current study a strategy of one-pot method by introducing Poly (lactic acid-carbonate) (PDT) and ß-Tricalcium Phosphate (ß-TCP) with SeNPs, is developed to prepare an injectable, anti-collapse, shape-adaptive and adhesive bone graft substitute material (PDT-TCP-SE). The PDT-TCP-SE bone graft substitute exhibits sufficient adhesion in biological microenvironments and osteoinductive activity, angiogenic effect and anti-inflammatory as well as anti-oxidative effect in vitro and in vivo. Moreover, the PDT-TCP-SE can protect BMSCs from erastin-induced ferroptosis through the Sirt1/Nrf2/GPX4 antioxidant pathway, which, in together, demonstrated the bone graft substitute material as an emerging biomaterial with potential clinical application for the future treatment of osteoporotic bone defect. STATEMENT OF SIGNIFICANCE: Injectable, anti-collapse, adhesive, plastic and bioactive bone graft substitute was successfully synthesized. Incorporation of SeNPs with PDT into ß-TCP regenerated new bone in-situ by moderating oxidative stress in osteoporotic bone defects area. The PDT-TCP-SE bone graft substitute reduced high ROS levels in osteoporotic bone defect microenvironment. The bone graft substitute could also moderate oxidative stress and inhibit ferroptosis via Sirt1/Nrf2/GPX4 pathway in vitro. Moreover, the PDT-TCP-SE bone graft substitute could alleviate the inflammatory environment and promote bone regeneration in osteoporotic bone defect in vivo. This biomaterial has the advantages of simple synthesis, biocompatibility, anti-collapse, injectable, and regulation of oxidative stress level, which has potential application value in bone tissue engineering.

The effect of type 2 diabetes mellitus on the prognosis of osteoporotic vertebral compression fracture with osteoporotic fracture classification after vertebroplasty.

BACKGROUND: To analyze the clinical and radiological effects of type 2 diabetes mellitus on the prognosis of osteoporotic vertebral compression fracture after percutaneous vertebroplasty, and explore the prognostic value of osteoporotic fracture classification. METHODS: Osteoporotic vertebral compression fracture patients who received vertebroplasty from January 1, 2016 to June 30, 2021 were divided into type 2 diabetes mellitus group and control group in this retrospective cohort study. Visual analogue scale, Oswestry Disability Index, bone cement leakage, new compression fracture, anterior, middle, and posterior portion heights of vertebral body and local Cobb angle on X-ray before surgery, 2 days after surgery, 6 months, and 12 months after surgery were recorded, and the osteoporotic fracture classification was performed. P < 0.05 was set as statistical significance. RESULTS: A total of 261 vertebral bodies were included, containing 68 in the type 2 diabetes mellitus group and 193 in the control group. There were no differences in baseline characteristics between the two groups. At 6 months after vertebroplasty, the local Cobb angle of the type 2 diabetes mellitus group was 8.29 ± 4.90° greater than that of the control group 6.05 ± 5.18° (P = 0.002). At 12 months, compared with pre-operation, the anterior portion height recovered 8.13 ± 12.90%, which was less than 12.51 ± 14.92% of the control group (P = 0.032), and 19.07 ± 16.47% of the middle portion height recovery was less than the control group's 24.63 ± 17.67% (P = 0.024). Compared with the control group, osteoporotic fracture 2 vertebral bodies of the type 2 diabetes mellitus group at 12 months postoperatively in middle portion height (14.82 ± 14.71% vs 24.78 ± 18.16%, P = 0.023) and local Cobb angle (5.65 ± 4.06° vs 3.26 ± 4.86°, P = 0.043) restored significantly worse. Besides, osteoporotic fracture 3 with type 2 diabetes mellitus restored worse in anterior portion height (5.40 ± 11.02% vs 13.57 ± 12.79%, P = 0.008), middle portion height (11.22 ± 15.53% vs 17.84 ± 12.36%, P = 0.041) and local Cobb angle (10.85 ± 3.79 vs 7.97 ± 3.83°, P = 0.002) at 12 months postoperatively. There was no difference in radiological outcomes of osteoporotic fracture 4 between the two groups. CONCLUSIONS: The degree of fractured vertebral compression, the recovery of the height and angle obtained immediately after surgery and the clinical symptoms in type 2 diabetes mellitus patients were not different from those in the control. However, vertebral body morphology of type 2 diabetes mellitus patients was worse since the sixth month after surgery. Osteoporotic fracture classification has a good prognostic reference value for both the control and the type 2 diabetes mellitus population.

Establishment and validation of an individualized nomogram to predict distant metastasis in chondrosarcoma patients: a population-based study.

Background: Distant metastasis is a significant factor influencing chondrosarcoma (CHS) patients' treatment and prognosis. We aimed to establish a consistent and effective nomogram to better predict distant metastases of CHS individuals. Methods: The Surveillance, Epidemiology and End Results (SEER) database was used to obtain the demographics and clinicopathological characteristics of CHS patients from 2010 to 2018. Independent risk factors were identified via univariate and multivariate logistic regressive analysis. A nomogram that predicts metastasis risk was established based on the training cohort, and its accuracy was validated through the validation cohort. The performance of this predictive model was assessed by the receiver operating characteristic (ROC) curve and Harrell's concordance index (C-index). Finally, decision curve analysis (DCA) was conducted to test its clinical reliability. Results: Data of 1,066 patients were extracted, of these, 66 cases (6.19%) were with distant metastasis at initial diagnosis. The following features were shown to be linked to an increased risk of metastasis: high-grade tumor, T3 stage, and large tumor size; whereas unmarried and use of surgery were independent protective factors. Marital status, tumor grade, T stage, use of cancer-directed surgery and tumor size were incorporated to develop the novel nomogram. The ROC curves showed the effectiveness of the nomogram with the high area under the curves, the C-indices were 0.931 and 0.951 in the internal and external validation, respectively. The calibration plots indicated a good consistency and agreement of the nomogram, while the DCA illustrated that the nomogram had favorable potential clinical applicability due to great positive net benefit with wide ranges of the threshold probabilities. Conclusions: This work developed a novel nomogram for predicting distant metastasis in CHS patients, which might assist clinicians to determine the optimal treatment plan by precisely predicting individualized metastatic risk.

The Effect of Daily Teriparatide versus One-Time Annually Zoledronic Acid Administration After Transforaminal Lumbar Interbody Fusion in Osteoporotic Patients.

PURPOSE: The research aimed to compare the therapeutic effect of teriparatide (TPTD) and zoledronic acid (ZOL) therapy on bone formation and spinal fusion in patients with osteoporosis (OP) who underwent transforaminal lumbar interbody fusion (TLIF). METHODS: On the basis of different anti-OP treatment options, the TPTD group was treated daily with TPTD (20 µg. ih. qd) for at least 6 months, while the ZOL group was treated with a single dose of ZOL (5 mg. ivgtt. st) postoperatively. The visual analogue scale (VAS), Oswestry Disability Index (ODI), bone mineral density (BMD), and concentration of bone turnover markers before, 6, and 12 months after surgery were evaluated. X-ray and three-dimensional computed tomography scans were performed at 6 and 12 months postoperatively to assess interbody fusion. RESULTS: The number of patients in the TPTD and ZOL groups was 29 and 38 patients, respectively. The VAS and ODI scores in both groups were significantly reduced at 6 and 12 months after TLIF. Compared with that of baseline, the lumbar spine BMD of TPTD patients increased significantly from 0.716±0.137 g/cm2 to 0.745±0.124 g/cm2 and 0.795±0.123 g/cm2 at 6 and 12 months, respectively, and was significantly higher than that of the ZOL group at 12 months (0.720±0.128 g/cm2). The bone formation marker, P1NP, in the TPTD group increased significantly (145.48±66.64 ng/mL and 119.55±88.27 ng/mL) compared with baseline (44.67±25.15 ng/mL) and in the ZOL group (28.82±19.76 ng/mL and 29.94±20.67 ng/mL) at 6 and 12 months, respectively. The fusion rates in the TPTD and ZOL groups were 57% and 45% at 6 months, without statistical significance. However, TPTD had a more statistically significant positive influence on fusion rate than ZOL at 12 months (86% vs 70%). CONCLUSION: TPTD was more efficient than ZOL in bone formation and spinal fusion in OP patients who underwent TLIF.